Bi-directional motion of a lorentz-force actuated needle-free injector (NFI)

ABSTRACT

The present invention relate to a method and corresponding apparatus for just in time mixing of a solid or powdered formulation and its subsequent delivery to a biological body. In some embodiments, a powdered formulation is maintained in a first chamber of a plurality of chambers. A plurality of electromagnetic actuators are in communication with the plurality of chambers. The actuators, when activated, generate a pressure within at least the first chamber. The pressure results in mixing of the powdered formulation and a diluent in time for delivering into the biological body.

RELATED APPLICATIONS

This application is a continuation of U.S. application Ser. No.12/960,405, filed Dec. 3, 2010, which is a continuation of U.S.application Ser. No. 12/879,787 filed Sep. 10, 2010, now U.S. Pat. No.8,398,583, which is a continuation-in-part of U.S. application Ser. No.12/712,824, filed Feb. 25, 2010, now abandoned, which is a continuationof U.S. application Ser. No. 12/459,866, filed Jul. 8, 2009, nowabandoned, which claims the benefit of U.S. Provisional Application No.61/134,344, filed on Jul. 9, 2008.

The entire teachings of the above applications are incorporated hereinby reference.

BACKGROUND OF THE INVENTION

Needle-free injection represents an alternative route for drugadministration that is free of many of the problems associated with theuse of needles (AntaresPharma 2005; Balzer et al. 2001). Needle-freeinjectors (NFIs) operate by creating a high pressure jet of fluid/powderthat penetrates the skin. Delivery is rapid (typically <0.5 s) whichreduces apprehension while enhancing patient acceptance and ultimatelycompliance. In addition, NFIs have been shown to improve the efficacy ofcertain medications (Taylor et al. 1981; Jackson et al. 2001; Williamset al. 2000). Current NFI injectors use springs or compressed inertgases to propel fluid through the skin and into the underlying tissue.This affords minimal control over the pressure applied to the drugduring the time course of the injection, parameters shown to be integralto determining the depth and dispersion of drug delivered (Wendell etal. 2006; Shergold et al. 2006), and hence its absorption into thecirculation. Others have incorporated some pressure pulse shaping byusing variable orifice gas valves or fast/slow pyrotechnic charges. Morerecently, Stachowiak et al. (2009) have used piezoelectric actuators fordynamic control of delivery, accomplished at the expense of a limitedpiston stroke and volume of fluid delivered.

An alternative approach to jet drug delivery is to store energy inelectrical form and impose a time varying pressure profile (waveform) onthe drug volume through the use of a monitored and servo-controlledelectromechanical actuator such as a linear Lorentz force actuator. Amoving coil Lorentz-force actuated NFI has been developed (U.S.application Ser. No. 11/354,279, filed Feb. 13, 2006 and published asU.S. Patent Publication No. 2007/0191758, the entire teachings of whichare incorporated by reference herein). The inherent bi-directionality ofthe actuator allows the applied pressure to be controlled and evenreversed when necessary.

SUMMARY OF THE INVENTION

An example embodiment of the present invention relates to a method andcorresponding apparatus for extraction of a sample from a sample source.The claimed method and apparatus relates to injecting a fluid into thesample source, vibrating the sample source and withdrawing a sample fromthe sample source, and evaluating the sample source as a function ofmeasuring one or more identifying parameters in the withdrawn sample.

The example embodiment may employ a bi-directional needle-free injectorto inject the fluid and withdraw the samples. The sample source mayinclude tissue of a biological body. The injected fluid may bephysiological saline. The withdrawn sample may be an extracellularfluid. The one or more identifying parameters may include metabolic orproteomic parameters.

The example embodiment may employ a dual actuated bi-directionalneedle-free injector to aspirate fluid from a medication vial or tissueor deliver fluid from one of two compartments within the device,subsequent mixing/reconstitution of the sample followed by injection ofdrug into a biological body.

Another example embodiment of the present invention relates to a methodand corresponding apparatus for delivering formulation to a biologicalbody. The apparatus includes a plurality of chambers and a plurality ofelectromagnetic actuators in communication with the plurality ofchambers. The plural chambers include a first chamber for holding apowdered formulation. The electromagnetic actuators, when activated,generate a pressure within at least one chamber of the plurality ofchambers that results in mixing of the powdered formulation and adiluent in time for delivering into the biological body.

The plurality of chambers may include a second chamber for holding thediluent for mixing with the powdered formulation.

Certain embodiments may include at least one valve connected to theplural chambers. For example, the at least one valve may include atleast two ports, a first port for passing the powdered formulation intothe first chamber anda second port for passing the diluent into thesecond chamber. Certain embodiments may further include a nozzle influid communication with the third port. The nozzle may be configured todeliver the resulting mixture near the distal end thereof into thebiological body.

In certain embodiments, the plurality of actuators, upon activation in areverse direction, may aspirate a diluent into at least one chamber ofthe plurality of chambers. At least one actuator of the plurality ofelectromagnetic actuators may aspirate the diluent from at least one ofa medication vial or a skin of a biological body following delivery offluid.

Certain embodiments may include at least one valve having a fluid pathto a fluid source. The valve, upon being opened, may deliver the diluentfor mixing with the powdered drug.

In certain embodiments the plurality of actuators, upon actuation, mayoscillate the contents of at least one chamber of the plurality ofchambers, resulting in mixing of the powdered formulation and thediluent in time for delivering into the biological body. The actuators,upon actuation, may deliver a mixture resulting from mixing of thepowdered formulation and the diluent into the biological body. Theactuator may be actuated using a preprogrammed waveform to deliver themixed drug into the biological body. In certain embodiments, the firstchamber may hold the diluent and the powdered formulation such that theyare separated by an air gap. Certain embodiments may include a sensorthat monitors displacement and volume of the powdered drug and thediluent in relation to the air gap.

In certain embodiments, a reservoir may be connected to the plurality ofchambers by at least one valve. The valve, when opened, may allowpressurized diluent to flow into the first chamber through the powderedformulation, resulting in fluidization of the powered formulation intime for delivering into the biological body

The diluent may be gas (such as hydrogen gas), water, or physiologicalsaline.

BRIEF DESCRIPTION OF THE DRAWINGS

The foregoing will be apparent from the following more particulardescription of example embodiments of the invention, as illustrated inthe accompanying drawings in which like reference characters refer tothe same parts throughout the different views. The drawings are notnecessarily to scale, emphasis instead being placed upon illustratingembodiments of the present invention.

FIG. 1 illustrates a handheld needle free injector that may be used inan example embodiment of the present invention.

FIG. 2 is an illustration of a cut-away view of the linear actuator of ahandheld needle free injector that may be used in an example embodimentof the present invention.

FIG. 3 is a high level illustration of an apparatus for extraction of asample from a sample source according to an example embodiment of thepresent invention.

FIG. 4 is a computer-aided design (CAD) drawing of a dual-actuatedneedle-free injector.

FIG. 5A-5B are schematics illustrating just in time mixing of asolid/powdered formulation (e.g., drug) using a dual actuatedneedle-free injector.

FIG. 6 is a schematic illustrating aspiration of fluid into the drugretention chamber by reversal of the actuator and therefore the pistonwhich is contiguous with the actuator to achieve just in time mixing.

FIG. 7A-7B are schematics showing reconstitution of powdered drug via anindependent fluid path or channel.

FIG. 8A-8B are schematics illustrating mixing of powdered drug and fluidseparated by an air gap.

FIG. 9A-9B are schematics showing fluidization of solid particulatematerial according to an example embodiment.

DETAILED DESCRIPTION OF THE INVENTION

A description of example embodiments of the invention follows.

This invention is related to articles and methods for injecting asubstance into an animal body. Needle-free injectors and actuators aredescribed in U.S. application Ser. No. 10/200,574, filed Jul. 19, 2002,which issued on Sep. 6, 2005 as U.S. Pat. No. 6,939,323, which claimsthe benefit of U.S. Provisional Application No. 60/338,169, filed Oct.26, 2001; U.S. application Ser. No. 10/657,734, filed Sep. 8, 2003,which is a Continuation of U.S. application Ser. No. 10/656,806 filedSep. 5, 2003, which claims the benefit of U.S. Provisional ApplicationNo's. 60/409,090, filed Sep. 6, 2002 and 60/424,114, filed Nov. 5, 2002;U.S. application Ser. No. 10/657,724, filed Sep. 8, 2003 which is aContinuation of U.S. application Ser. No. 10/656,806 filed Sep. 5, 2003which claims the benefit of U.S. Provisional Application No's.60/409,090, filed Sep. 6, 2002 and 60/424,114, filed Nov. 5, 2002; U.S.application Ser. No. 11/352,916 filed Feb. 10, 2006, which claims thebenefit of U.S. Provisional Application 60/652,483 filed Feb. 11, 2005;U.S. application Ser. No. 11/354,279 filed Feb. 13, 2006, which is aContinuation of U.S. application Ser. No. 11/352,916 filed Feb. 10, 2006which claims the benefit of U.S. Provisional Application No. 60/652,483,filed on Feb. 11, 2005; U.S. application Ser. No. 11/351,887 filed Feb.10, 2006 which claims the benefit of U.S. Provisional Application No.60/652,483 filed on Feb. 11, 2005; U.S. Provisional Application60/735,713 filed Nov. 11, 2005; U.S. application Ser. No. 11/598,556,filed on Nov. 13, 2006, which claims the benefit of U.S. ProvisionalApplication No. 60/735,713, filed on Nov. 11, 2005; U.S. applicationSer. No. 11/117,082, filed on Apr. 28, 2005, which is a continuation ofU.S. application Ser. No. 10/200,574, filed on Jul. 19, 2002, which isnow issued as U.S. Pat. No. 6,939,323, and International Application No.PCT/US2007/019247, filed on Aug. 31, 2007, which claims the benefit ofU.S. Provisional Application No. 60/841,794, filed on Sep. 1, 2006.

Further needle-free injectors and Lorentz-Force actuators are describedin an article, Taberner, A. J., Ball, N., Hogan, N. C., Hunter, I. W.,“A portable Needle-free Jet Injector Based on a Custom HighPower-Density Voice-coil Actuator,” Proceedings of the 28th AnnualInternational Conference of the IEEE EMBS, New York, N.Y., USA, August2006, 5001-5004.

The entire teachings of the above applications and articles areincorporated herein by reference.

An example embodiment of the present invention relates to a method andcorresponding apparatus that employs a needle-free injector (NFI) forthe extraction of sample from sources (e.g. tissue) following deliveryof fluid (e.g., physiological saline) using said device. Fluid isinjected into the sample source (for example the tissue), followed byvibration of the tissue using the tip of the ampule to promote mixingand finally removal of extracellular fluid in order to measure one ormore metabolic or proteomic parameters. This technology would use thebi-directional capability of the NFI and is dependent in part on theprinciples listed below:

-   -   a. Loading, delivery, and reloading of the ampule. Fluid can be        loaded into the ampule by reversing the polarity on the        amplifier which in turn reverses the motion of the moving coil        or voice coil causing it to move backwards retracting the        piston. Fluid is fired from the ampule by reversing the polarity        again causing the moving coil or voice coil and by extension the        piston to move forward after which it can be re-loaded and the        cycle repeated.    -   b. Use of a probe screwed into the front plate to measure skin        impedance. Impedance characteristics of biological soft tissues        are obtained by touching tissues with a small, hard, vibrating        probe and measuring the force response. Given the ease with        which the face plate holding the ampule can be        modified/interchanged, a probe could be attached to the face        plate and the moving coil or voice coil pulsed through a range        of frequencies while measuring the force response. This        information would be used to evaluate and/or choose an optimal        patient-specific waveform for delivery of fluid/drug using a        disposable commercially-available ampule of ˜300 uL (e.g. the        INJEX™ ampule, part #100100).    -   c. Use of the actuator to measure the viscoelastic properties of        the skin at the injection site immediately after injection of a        small volume of fluid (e.g. physiological saline). Fluid        remaining in the ampule is used to perturb the tissue by pulsing        the coil through a range of frequencies as described in item        “a.”    -   d. Use of a dual actuated device for just in time mixing of a        powder formulation followed by delivery.    -   e. Use of a dual actuated device for delivery of larger        therapeutic drugs at low pressure via a preexisting hole. One of        the two actuators delivers a small volume of fluid (e.g.        physiological saline) at a velocity sufficient to penetrate the        tissue followed by mixing of the remaining fluid with the        therapeutic and subsequent delivery of said therapeutic through        the hole created by the first injection.

FIG. 1 illustrates a handheld NFI 100 that may be used in an exampleembodiment of the present invention. The NFI 100 includes a disposablecommercially available 300 μL NFI INJEX™ ampule 130 attached to a customdesigned moving-coil Lorentz force actuator 110. The ampule 130 isscrewed into the front plate on the device and the piston is held by asnap-fitting on the front of the moving coil or voice coil 120. Thedesign of the front plate can be easily adapted to accept other ampules.The inherent bi-directionality of the moving-coil 120 allows drug to beeasily loaded into the ampule 130 prior to expulsion from the orifice.In certain embodiments, the orifice may have a diameter of 165 μm or 221μm and a piston diameter of 3.57 mm. The diameter of both the orificeand piston can be varied dependent on the drug and/or volume of drugbeing delivered.

In certain embodiments, the moving coil or voice coil 120 may include582 turns of 360 μm diameter polyvinyl butyral coated copper wire woundsix layers deep on a thin-walled Acetal copolymer former. This minimizesthe moving mass to approximately 50 g and avoids the drag caused byinduced eddy currents in a conducting former. The moving coil or voicecoil 120 slides on the inside of a 1026 carbon-steel extrusion that alsoforms the magnetic circuit. The latter consists of two 0.4 MN/m² (50MGOe) NdFeB magnets 225 inserted into the casing (Taberner et al. 2006).

The handheld NFI may further include an activation switch 140 that isused to activate the NFI, switch the NFI between ON/OFF positions,and/or activate the Lorentz force actuator. In certain embodiments, theactivation switch may function as a safety feature that is used to turnthe device on before each use.

In certain embodiments, the NFI may further include a housing 150 thatsurrounds the interior components of the injector. The NFI may furtherbe coupled with wires 160 that connect to a controller (not shown) thatcontrols various characteristics of the injections. For example, thecontroller may control various features (e.g., direction) of the movingcoil or voice coil actuator 110, injection characteristics such aspressure profile, speed, and etc.

FIG. 2 is a cut-away view of the linear actuator 110 of a handheldneedle free injector 200 that may be used in an example embodiment ofthe present invention.

In this embodiment, plastic-laminated, flexible copper ribbons form theelectrical connections to the moving coil or voice coil 120. A linearpotentiometer (not shown) mounted to a linear guide system (not shown)monitors the position of the moving coil or voice coil 120. In certainembodiments the moving coil or voice coil 120 may operate at a bandwidthof more than 1 kHz. The position sensor (not shown) may be coupled tothe voice coil 120 via a movable pin that is mounted on the leading edgeof the former. In certain embodiments, the system may be powered by a 4kW Techron amplifier, controlled by a PC-based data acquisition andcontrol system running in National Instruments LABVIEW™ 8.5 (Taberner etal. 2006).

The NFI may include an injection ampule 130. In some embodiments, theNFI may further include a nozzle to convey the substance through thesurface of the biological body at the required speed and diameter topenetrate the surface (e.g., skin). The nozzle generally contains a flatsurface, such as the head 115 that can be placed against the skin and anorifice 220. The nozzle 114 may be coupled to a syringe (not shown) orampule 130 defining a reservoir 113 for temporarily storing thetransferred substance. The syringe or ampule also includes a plunger orpiston 210 having at least a distal end slidably disposed within thereservoir. Movement of the plunger 210 along the longitudinal axis ofthe syringe or ampule 130 in either direction creates a correspondingpressure within the reservoir. As shown in FIG. 2, the NFI includesfront plate 230 and bearing surfaces 250.

The linear actuator 110 may further include a magnet assembly 225 thatincludes a column of magnets disposed along a central axis. The columnof magnets can be created by stacking one or more magnetic devices. Forexample, the magnetic devices can be permanent magnets. As a greatermagnetic field will produce a greater mechanical force in the same coil,thus stronger magnets are preferred. As portability and ease ofmanipulation are important features for a hand-held device 100,high-density magnets are preferred.

One such category of magnets are referred to as rare-earth magnets, alsoknown as Neodymium-Iron-Boron magnets (e.g., Nd₂Fe₁₄B). Magnets in thisfamily are very strong in comparison to their mass. Currently availabledevices are graded in strength from about N24 to about N54—the numberafter the N representing the magnetic energy product, inmegagauss-oersteds (MGOe). In one particular embodiment, N50 magnets areused.

The magnets are attached at one end of a casing 260 defining a hollowedaxial cavity and closed at one end. The casing 260 is preferably formedfrom a material adapted to promote containment therein of the magneticfields produced by the magnets. For example, the casing 260 may beformed from a ferromagnetic material or a ferrite. One suchferromagnetic material includes an alloy referred to as carbon steel(e.g., American Iron and Steel Institute (AISI) 1026 carbon steel).

In certain embodiments, the biological surface is stretched prior totransfer of the substance. First stretching the surface or skin permitsthe skin to be pierced using a lower force than would otherwise berequired. Stretching may be accomplished by simply pressing the nozzleinto the surface of the skin. In some embodiments, a separate surfacereference or transducer 240 is included to determine when the surfacehas been sufficiently stretched prior to transfer. Such a sensor canalso be coupled to a controller, prohibiting transfer until thepreferred surface properties are achieved.

In some embodiments, the NFI includes a transducer 240, such as adisplacement sensor used to indicate location of an object's coordinates(e.g., the coil's position) with respect to a selected reference.Similarly, a displacement may be used to indicate movement from oneposition to another for a specific distance. For example, the sensedparameter can be used as an indication of a change in the coil (120)position and hence the piston tip/plunger's (210) position. By extensionthis provides an indication of the volume or dose delivered. In someembodiments, as defined in the above example, a proximity sensor may beused to indicate when a portion of the device, such as the coil, hasreached a critical distance. Other types of sensors suitable formeasuring position or displacement could include inductive transducers,resistive sliding-contact transducers, photodiodes, andlinear-variable-displacement-transformers (LVDT). FIG. 3 is a high levelillustration of the system used for extraction of a sample from a samplesource according to an example embodiment of the present invention.

In this example embodiment 300, a bi-directional needle-free injectionsystem 310 injects a fluid into the sample source (e.g., a biologicalbody such as skin) The sample source is vibrated using the tip of theampule 312 or a probe screwed into the front plate of the actuator 311in place of the ampule by actuation of the moving coil or voice coil.The motion of the actuator is then reversed and the sample is removedfrom the sample source 314. The sample may be extracellular fluid. Asample evaluation module 317 evaluates the sample source as a functionof measuring one or more identifying parameters in the withdrawn sampleand outputs the evaluation results 318. The one or more identifyingparameters may include metabolic or proteomic parameters.

FIG. 4 is a computer-aided design (CAD) drawing of a dual-actuatedneedle-free injector 400 that may be used in an example embodiment ofthe present invention. In this example embodiment, fluid (e.g.,physiological saline) is delivered to the sample source (e.g., abiological body such as tissue) by one of two actuators 410. The samplemay be vibrated using the tip of the ampule 130 prior to aspiration offluid (e.g., extracellular fluid) from the sample injection site intothe second of two reservoirs 420 where it may be used to reconstituteanalytic components (e.g., enzyme, buffer, substrate) contained withinthe second reservoir and required for subsequent evaluation of thesample.

In certain embodiments, one of the two actuators 410 may be used todeliver an incremental volume of fluid (e.g., physiological salineaspirated from a medication vial or pre-filled) at a pressure, monitoredby a pressure transducer 430, sufficient to penetrate the sample sourcefollowed by mixing of the remaining fluid with a therapeutic held in thesecond reservoir. Reconstitution or mixing of the therapeutic using thedual actuated system would be followed by delivery through the holecreated by the first injection.

FIGS. 5A-5B are schematics 500A, 500B illustrating just in time mixingof a solid/powdered formulation (e.g., drug) using a dual actuatedneedle-free injector. As shown in FIG. 5A, fluid 509 and powdered drug510, each contained within a separate chamber are mixed by dualactuation using a three port valve 515. As shown in FIG. 5B, once mixed(shown as reconstituted powder 520), the valve is adjusted such that thedrug is delivered using one of the two actuators via an attached ampule130 to the biological body. Electromagnetic actuators 225 may be used inmixing of the fluid and the powdered drug. As shown in FIGS. 5A-5B, themoving coil or voice coils 120 may generate a pressure that results inmixing of the powdered drug/formulation and the diluent fluid in timefor delivering into the biological body.

FIG. 6 is a schematic 600 illustrating aspiration of fluid 509 into thedrug retention chamber by reversal of the moving coil or voice coil 120and therefore the piston 210 which is contiguous with the actuator toachieve just in time mixing. As shown in FIG. 6, fluid 509 is aspirated(for example, from vial 620 or from a biological body (not shown)) intothe drug retention chamber/ampule 130 by reversing the linearLorentz-force actuator 120 and therefore the piston 210. Further mixingof the powdered drug 510 and the fluid 509 is achieved by oscillation ofthe moving coil or voice coil 120 and by extension of the piston 210within a narrow voltage. Alternatively, mixing of the powdered drug 510and the fluid 509 may be achieved using an ultrasonic transducer (notshown) incorporated into the piston assembly. Once reconstituted, theappropriate volume of drug is ejected from the ampule 130 by actuationof the moving coil or voice coil 120 using a preprogrammed waveform. Anadapter 610 may be used to connect the vial to the NFI.

FIGS. 7A-7B are schematics 700A-700B showing reconstitution of powdereddrug 510 via an independent fluid path or channel. Diluent 509 may bedelivered to the chamber containing powdered drug 510 via an independentfluid path or channel using a valve 710 located at the proximal end ofthe ampule 130. Closure of the valve 710 after delivery of the desiredvolume would seal the channel from the drug reservoir 720. The drugreservoir 720 may be oscillated by actuation of the moving coil or voicecoil 120 using the electromagnetic actuators 225. The reconstituted drug520 (shown in FIG. 7B) is then delivered to a biological body throughthe nozzle 130 (initially covered by nozzle cap 730) in the direction ofinjection 750.

FIGS. 8A-8B are schematics 800A, 800B illustrating mixing of powdereddrug 510 and fluid 509 separated by an air gap. In certain embodiments,the powdered drug 510 and fluid 509 may be separated by an air gap 801in a single cassette. A sensor (not shown) may be utilized to monitordisplacement, the change in stroke, as defined by the fluid volume inthe chamber. Upon actuation of the electromagnetic actuator 225, thepiston 210 drives the fluid volume into the powder 510 resulting inmixing of the powder 510 and fluid 509 (which could be amplified byoscillation of the piston 210). Air could be purged from the chamber ina manner comparable to removing air from a conventional syringe afterwhich the reconstituted drug could be ejected through the ampule 130 andthe nozzle (shown in FIGS. 7A-7B) orifice by a second actuation in thedirection of injection 850.

FIGS. 9A-9B are schematics 900A and 900B showing fluidization of solidparticulate material (e.g., powdered drug 510) according to an exampleembodiment.

As shown in FIG. 9A, the solid particulate 510 is positioned in ampule130 above a perforated plate 910. Actuation of the voice coil and byextension movement of the piston 210 in the forward direction, forcesfluid (liquid or gas) 509 from a fluid/gas feed 911 up and through thesolid particulate 510, increasing velocity causing the particles toreach a critical state where they are suspended within the fluid 509.This fluid-like behavior allows the contents 920 to be ejected throughthe nozzle orifice in the direction of injection 900 and into abiological body.

While this invention has been particularly shown and described withreferences to example embodiments thereof, it will be understood bythose skilled in the art that various changes in form and details may bemade therein without departing from the scope of the inventionencompassed by the appended claims.

What is claimed is:
 1. A method for needle-free injection of a drugthrough a tissue into a biological body, the method comprising:providing the drug in a chamber of a needle-free injection device;providing a gas in the chamber; and after providing the drug and the gasin the chamber, using a bi-directional electromagnetic actuator to drivea piston in the chamber to (1) fluidize the drug in the gas inside thechamber, and (2) to eject the fluidized drug from the chamber through aneedle-free injection nozzle as a jet with sufficient pressure topenetrate the tissue of the biological body, wherein fluidizing the druginvolves oscillating the piston using the electromagnetic actuator tofacilitate fluidization of the drug in the gas.
 2. The method of claim1, wherein using the bi-directional electromagnetic actuator comprisesusing a bi-directional Lorentz-Force electromagnetic actuator.
 3. Themethod of claim 1, wherein the drug is a powdered drug.
 4. The method ofclaim 1, wherein the drug is a solid particulate material.
 5. The methodof claim 1, further comprising supporting the drug inside the chamber ona perforated plate prior to fluidizing the drug in the gas.
 6. Themethod of claim 1, wherein fluidizing the drug comprises using thebi-directional electromagnetic actuator to vibrate the gas inside thechamber to aid in fluidizing the drug in the gas.